This invention relates to cephalosporin antibiotics. In particular, it relates to cephalosporin antibiotics substituted in the 3'-position by a thienopyridinium group or a furopyridinium group and in the 7-position by an oxazole, isoxazole, and oxadiazole acetylamino group.
Cephalosporin semi-synthetic antibiotics substituted in the 3'-position by a quaternary ammonium group have been known for some time. For example, cephalosporin C.sub.A (pyridine) was one of the first derivatives of cephalosporin C prepared by Abraham et al., following the discovery of cephalosporin C, Hale, Newton, and Abraham, Biochem. J., 79, 403 (1961). Cephaloridine, which has achieved clinical importance, is the 3'-pyridinium compound, 7-(2-thienylacetamido)-3-(pyridinium-1-ylmethyl)-3-cephem-4-carboxylate, Flynn, U.S. Pat. No. 3,449,338.
Recently, 3'-quaternary substituted derivatives of some newer cephalosporins have been disclosed. For example, Takeda, U.K. Patent Specification No. 1,581,854, describes syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyoxyimino]-3-(pyridinium-1-ylmethyl )-3-cephem-4-carboxylate. O'Callaghan, et al., U.S. Pat. No. 4,258,041, describe syn-7-[2-(2-aminothiazol-4-yl)-2-(2-carboxyprop-2-yl)oxyiminoacetamido]-3- (pyridinium-1-ylmethyl)-3-cephem-4-carboxylate and the corresponding carbamoyl substituted pyridinium compounds. These 3'-pyridinium substituted cephalosporins are reported to be effective antibiotics against gram-negative bacteria.
Because of the continuing need for improved antibiotic therapy, the search continues for broad spectrum antibiotics with greater potency and minimal toxicity. The semi-synthetic cephalosporin antibiotics long have been recognized as broad spectrum antibiotics, and several have achieved clinical importance. Continued research with the cephalosporin antibiotics has centered of late on the development of antibiotics having higher activity against certain gram-negative microorganisms such as pseudomonas and those which produce .beta.-lactamases destructive of .beta.-lactam antibiotics.